State-of-the-art 2023 on gene therapy for phenylketonuria.
adeno-associated virus
gene editing
gene therapy
mRNA therapy
phenylalanine
phenylalanine hydroxylase
phenylketonuria
Journal
Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918
Informations de publication
Date de publication:
04 Jul 2023
04 Jul 2023
Historique:
revised:
13
06
2023
received:
30
03
2023
accepted:
30
06
2023
pubmed:
4
7
2023
medline:
4
7
2023
entrez:
4
7
2023
Statut:
aheadofprint
Résumé
Phenylketonuria (PKU) or hyperphenylalaninemia is considered a paradigm for an inherited (metabolic) liver defect and is, based on murine models that replicate all human pathology, an exemplar model for experimental studies on liver gene therapy. Variants in the PAH gene that lead to hyperphenylalaninemia are never fatal (although devastating if untreated), newborn screening has been available for two generations, and dietary treatment has been considered for a long time as therapeutic and satisfactory. However, significant shortcomings of contemporary dietary treatment of PKU remain. A long list of various gene therapeutic experimental approaches using the classical model for human PKU, the homozygous enu2/2 mouse, witnesses the value of this model to develop treatment for a genetic liver defect. The list of experiments for proof of principle includes recombinant viral (AdV, AAV, and LV) and non-viral (naked DNA or LNP-mRNA) vector delivery methods, combined with gene addition, genome, gene or base editing, and gene insertion or replacement. In addition, a list of current and planned clinical trials for PKU gene therapy is included. This review summarizes, compares, and evaluates the various approaches for the sake of scientific understanding and efficacy testing that may eventually pave the way for safe and efficient human application.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swiss National Science Foundation
ID : CRSII5_180257
Pays : Switzerland
Organisme : NIH HHS
Pays : United States
Organisme : Swiss National Science Foundation
ID : 310030-162547
Pays : Switzerland
Informations de copyright
© 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
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